Reduced levels of anabolic hormones can contribute to aging and frailty. Most studies that have investigated this focused on the relationship between individual hormones and specific age-associated diseases. An interesting study in older women aged 70-79 years sought to examine the associations of individual anabolic hormonal deficiencies of free testosterone, IGF-1 and DHEA, and to assess their combined effects as well.[1]

The odds of frailty for deficiency in each hormone individually, as well as for a count of all three hormones, was calculated. It was found that for each hormone, those with the deficiency were more likely to be frail than those without the deficiency, although this did not achieve statistical significance (free T: odds ratio 2.03; IGF-1: odds ratio 1.82; DHEAS: odds ratio 1.68). In contrast, those with two or three deficiencies had a very high likelihood of being frail with an odds ratio of 2.79, i.e. almost three times as likely of being frail.

Importance of diagnosing and treating multiple hormonal deficiencies

Both pre-frail and frail older women tend to have lower levels of anabolic hormones and are more likely to have deficiencies in multiple hormones than aged-matched non-frail women. The aggregate burden of hormonal deficiencies is an independent predictor of frailty, and the hormonal burden is more strongly associated with frailty than the type of hormonal deficiency.[1]

Interestingly, the hormones investigated in this study, testosterone, IGF-1 and DHEA, are from three distinctly regulated hormonal axes that in younger individuals fail simultaneously only in rare cases of pituitary dysfunction. Furthermore, IGF-1 and T have different receptors, each present in muscle, and a DHEAS receptor has never been cloned. However, there may be a biological link among these hormones beyond their individual axes, as muscle IGF-1 production is affected by T and DHEAS in part acts through its conversion to androgens.[2]

Other studies confirm this by showing that in elderly women over 66 years of age, even after adjusting for age, anthropometric measurements and physical activity, leg maximal muscle power correlated directly and similarly with IGF-1 and DHEA(S) levels. It was found that in healthy elderly women, lower values for maximal leg muscle power are related to lower circulating levels of both DHEAS and IGF-I.[3]

These findings underscore the importance of investigating all major hormones, and correcting deficiencies if present.[4-10] Given the known mechanisms of testosterone and GH/IGF-1 in building muscle (and possibly also DHEA in elderly) it is reasonable that age-related low levels of anabolic hormones contribute over time to sarcopenia and frailty.[2, 4, 5, 7, 10, 11] Thus, multiple small effects in aggregate can lead to adverse loss of muscle and disability. In this scenario, if replacement was to occur, it would require lower doses of multiple anabolic hormones [12]. In addition, multiple anabolic hormone replacement might also have beneficial synergistic effects.[13, 14]